Graft hyperperfusion in small-for-size grafts (SFSG) is considered the main causal factor of small-for-size syndrome (SFSS). We compared SFSG with a graft-to-recipient body ratio < or =0.8, with and without graft inflow modulation (GIM) by means of a hemi-portocaval shunt (HPCS). Thirteen patients underwent adult-to-adult living donor liver transplantation (AALDLT): G1, n = 5 [4 right livers (RL) and 1 left liver (LL)] without GIM, and G2, n = 8 (4 RL and 4 LL) with GIM. In G2 patients, portal vein flow (PVF) was significantly reduced by HPCS: 190 +/- 70 mL/min/100 g liver in G2 vs. 401 +/- 225 ml/min in G1 (p = 0.002). One- and 6-month post-transplantation graft volume/standard liver volume (GV/SLV) ratio was of 72% and 79.5% in G1; 80% and 101% in G2 (p = ns). SFSS was observed in three G1 recipients (who were retransplanted), but in none of the G2 patients. At 1-year, patient and graft survival was respectively of 40% and 20% in G1, 87.5% and 75% in G2 (p = 0.024 and 0.03). It is concluded that drastic reduction of PVF by means of HPCS improves overall patient and graft survival by averting the occurrence of SFSS. Graft inflow modulation through HPCS reduces the risk of complications when transplanting SFSG in adult recipients.

Size mismatching is a major concern in adult living donor liver transplantation (ALDLT). Graft hyperperfusion in these grafts is considered the main factor leading to graft dysfunction and poor survival. We describe the clinical significance of graft inflow modification (GIM) by splenic artery ligation in a series of 24 consecutive ALDLT. Between September 1999 and December 2001, 24 patients underwent ALDLT at our institution. Patients were divided into two groups: G1, n = 11 without GIM, and G2, n = 13 with GIM. Both groups were equivalent in terms of preoperative clinical state, graft characteristics, and surgical technique. Graft hyperperfusion was noticed overall, especially in small grafts (graft-to-recipient body weight ratio <0.8), with mean recipient portal vein (rPVF) values at least three times greater than those recorded in the donors. GIM permitted in G2 a significant decrease in rPVF. Small-for-size syndrome (SFSS) occurred in three (27%) patients in G1 with small grafts showing graft hyperperfusion and necessitating a retransplantation. SFSS did not occur in G2. One-year overall survival was 62% and 93% respectively for G1 and G2. It is concluded that when small-for-size grafts are accompanied by graft hyperperfusion, the rPVF should be lowered to avoid the SFSS and to improve the outcome. (Liver Transpl 2003;9:S36-S41.)

Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. Methods/Design: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 2^1/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. Trial Register: Trial registered at http://www.clinicaltrials.gov: NCT00355862 (EudraCT Number: 2005-005362-36)